Researchers have pinpointed a possible environmental component for autism spectrum disorder (ASD) that they say is linked to problems with an important group of enzymes known as topoisomerases. The enzymes can disrupt genes that can affect brain development in the womb.

University of North Carolina School of Medicine scientists published the finding in the journal Nature that they say is a major advancement toward finding an environmental factor that causes the disorder from disruption of genes related to brain development.

Topoisomerases may be more important than genes for neurodevelopment

Senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC said in a press release, "Inhibiting these enzymes has the potential to profoundly affect neurodevelopment -- perhaps even more so than having a mutation in any one of the genes that have been linked to autism."

Zylka adds exposure in the womb to a topoisomerase inhibitor “…has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development.”

In addition to chemotherapy drugs, antibiotics known as quinolones and fluoroquinalones also inhibit the enzymes. Popular examples include Cipro and Levaquin. It is important to note information about the drugs was not a part of Dr. Zylka's study and were not addressed or mentioned in the UNC press release.

In an telephone interview with EmaxHealth, Dr. Zylka said his team plans to look at other drugs that could be linked to autism through disruption of enzyme paths.

He also notes that quinolones and fluoroquinalone antibiotics target topoisomerase IV to stop bacterial replication inside of cells, in contrast to the chemotherapy drug used in the study that inhibits topoisomerase I, an enzyme necessary for DNA replication.

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Chemotherapy drug study gives clues to ASD

The research team came across the finding accidentally when they were studying the effects of the chemotherapy drug topotecan in mice and human nerve cells. They noticed the drug that is a topoisomerase-inhibitor interfered with the functioning of exceptionally long genes, just like genes associated with autism.

"That's when we had the 'Eureka moment,'" said Zylka. "We realized that a lot of the genes that were suppressed were incredibly long autism genes."

Topotecan suppressed 50 of the more than 300 genes associated with autism that the researchers say could lead to neurological problems seen with ASD.

The study, published in the journal Nature, pulls together more pieces of the autism puzzle. Zylka said the finding bridges the process of how genetic information translates into biological functions.

Approximately 20 percent of autism-linked genes are connected to synapses in the brain and another 20 percent have to do with gene transcription. The results of the accidental finding could mean autism does have an environmental component. The study could also mean better ways to detect and prevent ASD.

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